Do antidepressants during pregnancy increase baby’s autism risk?

Gut Check is a periodic look at health claims made by studies and by newsmakers. We ask: Should you believe this?

The Claim: Using antidepressants during pregnancy, especially in the second or third trimesters, “increases the risk of autism,” reports a paper published on Monday in JAMA Pediatrics.

The Backstory: Suspicions of a link between antidepressants and autism aren’t new. A 2013 study using data from Sweden and 2014 research using data from Denmark both found an increased risk of autism among children exposed to antidepressants in the womb. Two others from Denmark, here and here, found no statistically significant link. Neither did a 2014 study from researchers at Massachusetts General Hospital — though this one did find an association between prenatal exposure to antidepressants and attention deficit hyperactivity disorder.

Even studies that find an increased risk of autism from prenatal exposure to antidepressants caution that it’s not clear what the cause is, the drugs or the depression or some unknown factor. Few studies include a crucial third group — severely depressed women who do not take antidepressants while pregnant — which would help untangle the role of those two effects. And as the Swedish study warned, even “assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly to the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.”

Some 5 percent of all babies born in the United States, or 200,000 a year, are exposed to antidepressants in the uterus. While 1 in 150 US children born in 1992 have been diagnosed with autism, 1 in 68 born in 2002 have been.

First Take: The new study is based on records of 145,456 full-term births in Quebec from 1998 to 2009. That puts it on the smaller side (the 2013 Denmark study had quadruple that number). Following the children for an average of six years, researchers led by Anick Bérard of the University of Montreal counted 1,054 with a diagnosis of autism. Among mothers who filled at least one prescription for antidepressants during their second and/or third trimester, the risk of having an autistic child was 1.87-fold higher. Taking SSRIs — selective serotonin reuptake inhibitors, such as fluoxetine (Prozac) or paroxetine (Paxil) — as opposed to another kind of antidepressant was associated with 2.17 times the risk.

The researchers used standard statistical analyses to separate out factors such as maternal age, poverty, and age at conception, which might make a woman more likely to have a child with autism. Bérard, who has testified for families in lawsuits claiming that antidepressants caused birth defects, called the link to SSRIs “biologically plausible.” The drugs affect the availability of the neurochemical serotonin, which is involved in numerous steps in brain development.

Second Take: The University of Montreal’s news release on the study said taking antidepressants during pregnancy “greatly increases” the risk of autism; it also quotes Bérard as saying the research “established that taking antidepressants during the second or third trimester of pregnancy almost doubles” the risk of autism.

Please. In no way did the study “establish” that. The most it did was show an association between taking antidepressants and having a child diagnosed on the autism spectrum. Prenatal antidepressants might cause autism, or they might not. Maybe a third factor causes both antidepressant use and having an autistic child. “You’re right,” Bérard told STAT. “We can’t say it’s a causal effect from any individual study.”

Outside experts caution that the key third factor might be differences between pregnant women with a psychiatric illness (SSRIs are also prescribed for anxiety and other mental disorders) who continue taking the drugs and those who stop. That is, some unknown characteristic of pregnant women who don’t or can’t stop taking antidepressants might independently raise the risk that their children will have autism.

“They weren’t able to say whether women who do not stop taking an antidepressant during pregnancy have a more severe form of depression and possibly a different disorder entirely, than women who stop,” Dr. Bryan King, a psychiatrist and autism expert at Seattle Children’s Hospital, said in an interview. “It’s not a huge leap to ask if they’re seeing an effect not from antidepressants but from the underlying disorder.”

One reason that’s plausible is that depression and autism appear to share genetic causes, a 2014 study found. Indeed, in the 2014 MGH study, the researchers initially found what appeared to be a connection between antidepressant use during pregnancy and having a child on the autism spectrum, but the link disappeared after the researchers took into account the severity of the mothers’ depression.

That is not to dismiss the possibility that prenatal exposure to antidepressants itself increased the risk of autism. But any increased risk was small, despite that “almost doubles” sound bite. In real numbers, of 2,532 children exposed to antidepressants during mom’s second or third trimester, 31 had autism; 2,501 did not. That works out to “an additional 12 children” with autism than expected, King wrote in an editorial.

One additional case of autism is one too many, King emphasized, so if antidepressants are responsible that’s important to know. But we don’t know it yet.

That leaves pregnant women suffering from depression between a rock and a hard place. While SSRIs might harm their fetus, untreated depression has been linked to prenatal stress, low birth weight, and prematurity, said maternal-fetal medicine expert Dr. Alison Stuebe of the University of North Carolina. It can also increase a pregnant woman’s production of stress hormones that cause lifelong harms to her child’s brain plasticity (the basis of learning) and cognition, a recent study reported.

But more and more experts argue that “suffer depression” vs. “harm your baby” is a false trade-off. Among pregnant women with depression, some 85 percent are mildly or moderately depressed, Bérard said. For these forms of depression, the response to SSRIs is almost solely due to a placebo effect, numerous studies and a large meta-analysis have shown. Exercise, psychotherapy, and other non-drug therapies are also effective and pose no risk of autism. “Offering an alternative to medication, especially for mild or moderate depression, would be a very good approach,” said Dr. Alan Brown, professor of psychiatry and epidemiology at Columbia University Medical Center.

The Takeaway: The new study adds to evidence that prenatal exposure to antidepressants might increase the risk of autism, but falls short of proving that; if there is an increased risk, in absolute terms it is very small.